Construction And Prognostic Value Assessment Of A New Staging System For Colorectal Cancer Based On Lymph Node Ratio

PurposeTNM staging system established by the American Joint Committee on Cancer(AJCC)and the International Union against Cancer(UICC)is the main basis for clinical/pathological staging of patients with colorectal cancer(CRC).It is widely used in predicting the prognosis of patients with CRC,and also serves as the basis for guiding postoperative chemotherapy.In the TNM staging system,CRC patients will only be classified into stage Ⅲ if they have positive lymph node metastasis.This rule badly has been underestimating the T stage prognosis weight.In the TNM staging system not only exists "survival paradox" that makes it independent of clinical prognosis,but also the quality standard for adequate staging of at least 12 lymph nodes fails to remove the impact of "stage migration".The main purpose of this study is through reconsidering the T stage,to build new TLnrM colorectal cancer clinical staging system which based on LNR(Lymph Node radio),to eliminate the phenomenon of"survival paradox",and fill the blank of predicting the prognosis of patients with CRC whose lymph node yield below the quality standard,ultimately achieve the purpose of more accurate to predict the prognosis of patients with CRC.MethodsData from 60,991 patients with first primary colorectal cancer who were diagnosed and underwent surgical treatment from 2010 to 2015 in the SEER database were selected as the training set to establish a novel TLnrM clinical staging system for colorectal cancer.The clinicopathological data of 954 colorectal patients who were first diagnosed and received surgical treatment from June 2012 to December 2016 in Jiangsu People’s Hospital Affiliated to Yangzhou University were included as the external validation set.Harrell’s Concordance Index(C-index),Area Under the Curve of Receiver Operating Characteristic(AUC)and Akaike Information criteria(AIC)were used to compare and analyze the prediction accuracy and good fit between TLnrM staging system and the 8th edition TNM staging system.The lower the AIC value,the higher the AUC value and the higher the C-index value,the better the performance of the staging system.For C-index value,the TLnrM staging system was higher than the TNM staging system in internal validation,while the TLnrM staging system was lower than the TNM staging system in external validationResult"Survival paradox" indeed exists in the eighth edition of TNM staging,patients with stageⅢA diseases have superior prognosis to patients with stage ⅡB/C diseases,and even the prognosis of patients with stage ⅢB diseases are superior to patients with stage Ⅱ B/C diseases,"survival paradox" phenomenon also exists in the group with lymph node yield<12.Multi-factor analysis show that both AJCC 8th N staging and Lnr staging are independent risk factors for prognosis in patients with colorectal cancer.The HR of Lnr stage is higher than AJCC 8th N stage(1.23 vs 1.13).Compared with the N staging,the AIC value of Lnr stage is relatively low(324782.5743 vs.325906.9857),but C-index value is higher(0.7650 vs.0.7461).The new TLnrM staging system does not have the phenomenon of "survival paradox",and has better goodness of fit and accuracy as well as the TNM staging system.For AIC value,regardless of internal or external validation,the TLnrM staging system is lower than the TNM staging system,especially in the group with lymph node yield<12 in internal validation.For C-index value,the TLnrM staging system is higher than the TNM staging system in internal validation,while the TLnrM staging system is lower than the TNM staging system in external validation.For the AUC value of the area under the ROC curve,the TLnrM staging system is higher than the TNM staging system in the internal validation of the whole data,but the TLnrM staging system is lower than the TNM staging system in the internal validation of lymph node yield<12 groups and external validation.Conclusion1.The "survival paradox" does exist in the TNM staging system,not just involves in stage ⅡB/C and stage ⅢA,but even involves in stage ⅡA and stage ⅢB.2.Compared with N staging,Lnr staging had better subgroup differentiation ability.3.The new TLnrM staging system successfully eliminates the "survival paradox",the ability to distinguish prognosis of CRC patients is not inferior to that of TNM staging,and can achieve accurate prognosis assessment of CRC patients whose lymph node examination is below the quality standard,so it has certain clinical applicability.